Abstract
The UNC-51 serine/threonine kinase of C. elegans plays an essential role in axonal elongation, and unc-51 mutants exhibit uncoordinated movements. We have previously identified mouse and human cDNAs encoding UNC-51-like kinase (ULK1). Here we report the identification and characterization of the second murine member of this kinase family, ULK2. Mouse ULK2 cDNA encodes a putative polypeptide of 1033 aa which has an overall 52% and 33% amino acid identity to ULK1 and UNC-51, respectively. ULKs and UNC-51 share a typical domain structure of an amino-terminal kinase domain, a central proline/serine rich (PS) domain, and a carboxy-terminal (C) domain. Northern blot analysis showed that ULK2 mRNA is widely expressed in adult tissues. In situ hybridization analysis indicated that ULK2 mRNA is ubiquitously localized in premature as well as mature neurons in developing nervous system. ULK2 gene was mapped to mouse chromosome 11B1.3 and rat chromosome 10q23 by FISH. HA-tagged ULK2 expressed in COS7 cells had an apparent molecular size of ∼150 kDa and was autophosphorylated in vitro. Truncation mutants suggested that the autophosphorylation occurs in the PS domain. Although expression of ULK2 failed to rescue unc-51 mutant of C. elegans, a series of ULK2/UNC-51 chimeric kinases revealed that function of the kinase and PS domains are conserved among species, while the C domain acts in a species-specific manner. These results suggest that ULK2 is involved in a previously uncharacterized signaling pathway in mammalian cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Chen W, Chen S, Yap SF and Lim L. . 1996 J. Biol. Chem. 271: 26362–26368.
Chervitz SA, Aravind L, Sherlock G, Ball CA, Koonin EV, Dwight SS, Harris MA, Dolinski K, Mohr S, Smith T, Weng S, Cherry JM and Botstein D. . 1998 Science 282: 2022–2028.
Cohen P. . 1992 Trends Biochem. Sci. 17: 408–413.
Desai C, Garriga G, McIntire SL and Horvitz HR. . 1988 Nature 336: 638–646.
Gross RE, Bagchi S, Lu X and Rubin CS. . 1990 J. Biol. Chem. 265: 6896–6907.
Hanks SK and Hunter T. . 1995 FASEB J. 9: 579.
Hedgecock EM, Culotti JG, Thomson JN and Perkins LA. . 1985 Dev. Biol. 111: 158–170.
Hunter T. . 1987 Cell 50: 823–829.
Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N and Ohara O. . 1998 DNA Res. 5: 169–176.
Kozak M. . 1986 Cell 44: 283–292.
Kuroyanagi H, Yan J, Seki N, Yamanouchi Y, Suzuki T, Takano T, Muramatsu M and Shirasawa T. . 1998 Genomics 51: 76–85.
Land M, Islas-Trejo A, Freedman JH and Rubin CS. . 1994 J. Biol. Chem. 269: 9234–9244.
Matsuda Y, Harada Y, Natsume-Sakai S, Lee K, Shiomi T and Chapman VM. . 1992 Cytogenet. Cell Genet. 61: 282–285.
Matsuda Y and Chapman VM. . 1995 Electrophoresis 16: 261–272.
Matsuura A, Tsukada M, Wada Y and Ohsumi Y. . 1997 Gene 192: 245–250.
McIntire SL, Garriga G, White J, Jacobson D and Horvitz HR. . 1992 Neuron 8: 307–322.
Mello CC, Kramer JM, Stinchcomb D and Ambros V. . 1991 EMBO J. 10: 3959–3970.
Ogura K, Wicky C, Magnenat L, Tobler H, Mori I, Muller F and Ohshima Y. . 1994 Genes Dev. 8: 2389–2400.
Ogura K, Shirakawa M, Barnes TM, Hekimi S and Ohshima Y. . 1997 Genes Dev. 11: 1801–1811.
Paradis S and Ruvkun G. . 1998 Genes Dev. 12: 2488–2498.
Shirasawa T, Akashi T, Sakamoto K, Takahashi H, Maruyama N and Hirokawa K. . 1993 Dev. Dyn. 198: 1–13.
Tabuse Y, Nishiwaki K and Miwa J. . 1989 Science 243: 1713–1716.
Tatusov RL, Koonin EV and Lipman DJ. . 1997 Science 278: 631–637.
Takeshige K, Baba M, Tsuboi S, Noda T and Ohsumi Y. . 1992 J. Cell. Biol. 119: 301–311.
Tsukada M and Ohsmumi Y. . 1993 FEBS Lett. 333: 169–174.
Watkins-Chow D, Roller M, Newhouse MM, Buchberg AM and Champer SA. . 1996 Mammal. Genome 6: S201–S220.
Way JC and Chalfie M. . 1988 Cell 54: 5–16.
Yamada J, Kuramoto T and Serizawa T. . 1974 Mammal. Genome 5: 63–83.
Yan J, Kuroyanagi H, Kuroiwa A, Matsuda Y, Tokumitsu H, Tomoda T, Shirasawa T and Muramatsu M. . 1998 Biochem. Biophys. Res. Comm. 246: 222–227.
Acknowledgements
J Yan and H Kuroyanagi made equal contributions in this study. We thank Y Fujita for the photographical assistance.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yan, J., Kuroyanagi, H., Tomemori, T. et al. Mouse ULK2, a novel member of the UNC-51-like protein kinases: unique features of functional domains. Oncogene 18, 5850–5859 (1999). https://doi.org/10.1038/sj.onc.1202988
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202988
Keywords
This article is cited by
-
Autophagy-related DjAtg1-1 plays critical role in planarian regeneration by regulating proliferation and cell death
Cell and Tissue Research (2022)
-
GSK3B induces autophagy by phosphorylating ULK1
Experimental & Molecular Medicine (2021)
-
Involvement of Nuclear Receptor REV-ERBβ in Formation of Neurites and Proliferation of Cultured Adult Neural Stem Cells
Cellular and Molecular Neurobiology (2018)
-
Autophagy core machinery: overcoming spatial barriers in neurons
Journal of Molecular Medicine (2016)
-
Autophagy signal transduction by ATG proteins: from hierarchies to networks
Cellular and Molecular Life Sciences (2015)